Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway

DU Wei; YANG Yufang; LIAO Yanhong; ZOU Xiaoqin; LIANG Zhiwei; FENG Xiangqian; ZHONG Xiaobin

doi:10.6039/j.issn.1001-0408.2026.12.05

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Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway

更新时间：2026-06-26

- Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway
- ZHONGGUO YAOFANG Vol. 37, Issue 12, Pages: 1547-1552(2026)
- 作者机构：
  
  1.广西医科大学药学院，南宁　530021
  2.广西医科大学第一附属医院药学部，南宁　530021
  3.广西医科大学第一附属医院科研部，南宁　530021
  4.广西医科大学附属肿瘤医院临床药学部，南宁　530012
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.12.05
  CLC： R965
- Received：04 January 2026，
  
  Revised：2026-06-13，
  
  Accepted：15 June 2026，
  
  Published：30 June 2026
- 稿件说明：
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杜炜,杨玉芳,廖燕红,等.肾福康胶囊通过STAT3/YAP通路调控细胞串扰改善肾间质纤维化的机制[J].中国药房,2026,37(12):1547-1552.

DU Wei,YANG Yufang,LIAO Yanhong,et al.Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway[J].ZHONGGUO YAOFANG,2026,37(12):1547-1552.
杜炜,杨玉芳,廖燕红,等.肾福康胶囊通过STAT3/YAP通路调控细胞串扰改善肾间质纤维化的机制[J].中国药房,2026,37(12):1547-1552. DOI： 10.6039/j.issn.1001-0408.2026.12.05.

DU Wei,YANG Yufang,LIAO Yanhong,et al.Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway[J].ZHONGGUO YAOFANG,2026,37(12):1547-1552. DOI： 10.6039/j.issn.1001-0408.2026.12.05.

摘要

目的

探讨肾福康胶囊（SFK）通过信号转导及转录活化因子3（STAT3）/Yes相关蛋白（YAP）通路调控巨噬细胞-成纤维细胞串扰改善肾间质纤维化（RIF）的作用机制。

方法

用转化生长因子β

（TGF-β

）诱导巨噬细胞RAW264.7极化，再建立巨噬细胞与肾成纤维细胞NRK-49F的非接触共培养体系，以及巨噬细胞与YAP敲低肾成纤维细胞非接触共培养体系，给予低、中、高浓度（4、8、16 μg/mL）SFK，以及STAT3抑制剂（STAT3-I，1.64 μg/mL）、氯沙坦钾片（阳性对照，0.28 μg/mL），干预48 h。检测巨噬细胞中CD86、CD163、STAT3蛋白和CD86、F4/80、STAT3 mRNA表达水平，共培养肾成纤维细胞中

平滑肌肌动蛋白（

-SMA）、波形蛋白（Vimentin）、Ⅰ型胶原（Col-Ⅰ）、基质金属蛋白酶1（MMP-1）、YAP蛋白及mRNA表达水平，以及共培养YAP敲低肾成纤维细胞中

-SMA、Vimentin、MMP-1蛋白及mRNA表达水平。

结果

TGF-β

诱导后巨噬细胞中CD86、CD163、STAT3蛋白表达水平和CD86、F4/80、STAT3 mRNA表达水平均显著升高（

＜0.05）；极化的巨噬细胞的培养液可激活肾成纤维细胞，使肾成纤维细胞中

-SMA、Vimentin、Col-Ⅰ、YAP蛋白及mRNA表达水平均显著升高，MMP-1蛋白及mRNA表达水平显著降低（

＜0.05）；SFK、STAT3-I可逆转以上指标的变化，其中SFK中浓度组部分指标效果强于SFK低、高浓度组。在巨噬细胞与YAP敲低肾成纤维细胞非接触共培养实验中，各组细胞中

-SMA、Vimentin、MMP-1蛋白及mRNA表达差异均无统计学意义。

结论

SFK可通过阻断STAT3/YAP通路，抑制巨噬细胞-肾成纤维细胞串扰，从而延缓RIF进展。

Abstract

OBJECTIVE

To investigate the mechanism by which Shenfukang capsule （SFK） ameliorates renal interstitial fibrosis （RIF） by regulating macrophage-fibroblast crosstalk via the signal transducer and activator of transcription 3 （STAT3）/Yes-associated protein （YAP） pathway.

METHODS

RAW264.7 macrophages were induced to polarize with transforming growth factor-β

（TGF-β

）. Subsequently， a non-contact co-culture system of macrophages with renal fibroblasts NRK-49F， as well as a non-contact co-culture system of macrophages with YAP-knockdown renal fibroblasts， were established. Cells were treated with low， medium， and high concentrations （4， 8， 16 μg/mL） of SFK， as well as a STAT3 inhibitor （STAT3-I，1.64 μg/mL） and losartan potassium tablets （positive control， 0.28 μg/mL）， for 48 h. After intervention， the protein and mRNA expression levels of CD86， CD163， and STAT3 in macrophages， as well as CD86， F4/80， and STAT3 mRNA， were detected. In co-cultured renal fibroblasts， the protein and mRNA expression levels of

-smooth muscle actin （

-SMA）， Vimentin， collagen type Ⅰ （Col-Ⅰ）， matrix metalloproteinase-1 （MMP-1）， and YAP were detected. In co-cultured YAP-knockdown renal fibroblasts， the protein and mRNA expression levels of

-SMA， Vimentin， and MMP-1 were also detected.

RESULTS

Following TGF-β

induction， the protein expression levels of CD86， CD163， and STAT3， as well as the mRNA expression levels of CD86， F4/80， and STAT3 in macrophages were significantly increased （

＜0.05）. The conditioned medium from polarized macrophages activated renal fibroblasts， as evidenced by significantly increased protein and mRNA expression levels of

-SMA， Vimentin， Col-Ⅰ， and YAP， and significantly decreased protein and mRNA expression levels of MMP-1 in renal fibroblasts （

＜0.05）. Treatment with SFK and STAT3-I reversed the changes in the above indicators， with the medium concentration SFK group showing stronge

r effects on some indicators than the low and high concentration groups. In the non-contact co-culture experiment of macrophages and YAP-knockdown renal fibroblasts， there were no statistically significant differences in the protein and mRNA expression of α-SMA， Vimentin， and MMP-1 among the groups.

CONCLUSIONS

SFK can inhibit macrophage-renal fibroblast crosstalk by blocking the STAT3/YAP pathway， thereby delaying the progression of RIF.

关键词

Keywords

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